Laparoscopic contrast enhanced ultrasound for cancer detection

胰腺癌在英国最常见的癌症中排名第十，其发病率在过去40年中增加了30%，但5年生存率一直很低，约为8%，在同一时期没有改善。目前，只有大约10%的患者适合手术。更早发现疾病可以增加癌症仍然适合手术切除的患者数量，从而对患者的预后起到重要作用。那些肿瘤无法触及或太过晚期而无法手术的患者依赖于化疗或免疫治疗。然而，胰腺导管癌的特点是形成致密的纤维间质和富含胶原的细胞外基质，这严重限制了可用于治疗它的药物的渗透。这导致了人们对能够针对这种致密的间质进行治疗的治疗方法的开发产生了相当大的兴趣。我们的团队正在开发能够更好地对间质进行成像的工具，以支持早期诊断和微创治疗。这集中在新的造影剂以提高成像灵敏度，但这些新的成像增强和功能的全部潜力只有随着新的超声硬件和换能器的出现才能有效地实现。为了改善患者的预后，迫切需要一种新的超声换能器，这种换能器可以在内窥镜或腹腔镜下进入组织，以提供更灵敏的成像来检测癌症中微尺度的组织变化。光声成像是基于激光超声的一种新兴的生物医学成像方式。与常规超声相比，PA成像能够提供软组织的功能信息，用于治疗监测和肿瘤检测。研究了US/PA双模成像技术，并将其应用于PA显微镜。近年来，在导管设计、换能器配置和扩展功能方面，这种双模式成像已被用于血管内和内窥镜应用的微型换能器和导管。腹腔镜PA成像设备的开发是一个新的课题，目前仅有少数几个原型设计的报道。还有相当大的机会进一步提高设备规格，包括尺寸和性能。本项目将从理论和实验两个方面研究先进的腹腔镜PA装置的发展。这种多模式成像的实现将通过与US4US的合作得到进一步的支持，US4US专门从事新产品开发，提供能够操作我们的设备以提供新型超声成像应用的驱动系统。该项目将受益于与另一个FUSE项目以及包括胰腺癌专家在内的学者研究小组的合作，这些研究小组都参与了这些项目。其结果将是优化了胰腺对比增强成像的新的腹腔镜设备，以提供更好的和更早的疾病检测用于治疗和改善患者的结果。确定用于设计腹腔镜PA装置的成像机制、装置配置和材料2。模拟US换能器和光学设置，从理论上评估和辅助器件性能的设计3。制造和表征超声换能器，用于拟议的腹腔镜式PA装置。通过模体评估已开发设备的基本PA成像性能，例如分辨率、光通量和信噪比5。通过体外和体内研究，评估所开发的设备的成像性能。

Pancreatic cancer is the tenth most common cancer in the UK, with an incidence that has increased by 30% over the last 40 years but persistently low 5-year survival of approximately 8% that has not improved over the same time period. Currently only around 10% of patients are suited to surgery. Earlier detection of disease could play a significant role in patient outcomes by increasing the number of patients whose cancer remains suited to surgical resection. Those patients whose tumour is not accessible or too advanced for surgery are reliant on chemotherapy or immune-therapy treatments. However, pancreatic ductal carcinoma is characterised by the evolution of a dense fibrotic stroma and collagen-rich extra-cellular matrix that can severely limit the penetration of drugs available to treat it. This has led to considerable interest in the development of therapeutics that can target this dense stroma to enable treatment. Our group is working on developing tools that can allow better imaging of stroma to support earlier diagnosis and minimally invasive treatments. This has focussed on new contrast agents to improve imaging sensitivity, but the full potential of these new imaging enhancement and functionality can only be effectively realised with the advent of new ultrasound hardware and transducers to exploit them. New ultrasound transducers that can access tissues endo- or laparoscopically to deliver imaging more sensitive to the detection of microscale tissue alterations in cancer are urgently required to improve patient outcomes. Photoacoustic (PA) imaging is an emerging biomedical imaging modality based on laser-generated US. Compared to conventional US, PA imaging is capable of providing functional information of soft tissue for treatment monitoring and tumor detection. The US/PA dual-modality imaging has been studied and employed for PA microscopy. In recent years, such dual-modality imaging has been implemented with miniature transducers and catheters for intravascular and endoscopic applications in terms of catheter design, transducer configuration, and extended functions. The topic of laparoscopic PA imaging device development is further new, in which only a few prototype designs have been reported. There remains considerable opportunity to further enhance the device specifications including size and performance. This project will investigate the development of advanced laparoscopic PA devices using both theoretical and experimental approaches. Realization of such multi-modal imaging will be further supported through collaboration with US4US, who specialize in new product development providing the drive systems that capable of operating our devices to deliver novel ultrasound imaging applications. This project will benefit from association with another FUSE project and the research groups of the academics, including pancreatic cancer experts, involved across each of these. The outcome will be new laparoscopic devices optimised for contrast enhanced imaging of the pancreas to deliver better and earlier detection of disease for treatment and improved patient outcomes.Key Objectives1. To identify the imaging mechanisms, device configuration, and materials for the design of a laparoscopic PA device2. To simulate the US transducers and optical setup to theoretically estimate and aid design of device properties3. To fabricate and characterize US transducers for the proposed laparoscopic PA device4. To evaluate the basic PA imaging performance, say resolution, optical fluence and signal-to-noise ratio, of developed devices via phantoms5. To evaluate the imaging performance of developed devices via ex vivo and in vivo studies.